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    The EU Clinical Trials Register currently displays   38482   clinical trials with a EudraCT protocol, of which   6323   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-001172-15
    Sponsor's Protocol Code Number:APN01-01-COVID19
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-03-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedAustria - BASG
    A.2EudraCT number2020-001172-15
    A.3Full title of the trial
    Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19
    Rekombinantes humanes Angiotensin-konvertierendes Enzym 2 (rhACE2) als Behandlung für Patienten mit COVID-19
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19
    Rekombinantes humanes Angiotensin-konvertierendes Enzym 2 (rhACE2) als Behandlung für Patienten mit COVID-19
    A.3.2Name or abbreviated title of the trial where available
    APN01-01-COVID19
    A.4.1Sponsor's protocol code numberAPN01-01-COVID19
    A.5.4Other Identifiers
    Name:INDNumber:151312
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAPEIRON Biologics AG
    B.1.3.4CountryAustria
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAPEIRON Biologics AG
    B.4.2CountryAustria
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAPEIRON Biologics AG
    B.5.2Functional name of contact pointSponsor
    B.5.3 Address:
    B.5.3.1Street AddressCampus-Vienna-Biocenter 5
    B.5.3.2Town/ cityVienna
    B.5.3.3Post code1030
    B.5.3.4CountryAustria
    B.5.6E-mailsonja.hoeller@apeiron-biologics.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRecombinant human angiotensin-converting enzyme 2
    D.3.2Product code APN01
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAPN01 / GSK2586881
    D.3.9.3Other descriptive nameGSK2586881
    D.3.9.4EV Substance CodeSUB83581
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Severe COVID-19 POSITIVE hospitalized male or female, between 18 and ≤ 80 years of age
    Stationäre, positiv getestete weibliche oder männliche COVID-19 Patienten mit schwerem Verlauf; Alter zwischen 18 und 80 Jahren
    E.1.1.1Medical condition in easily understood language
    Hospitalised Severe Covid-19 positive tested patients between 18 and 80 years old
    Stationäre, positiv getestete weibliche oder männliche COVID-19 Patienten mit schwerem Verlauf; Alter zwischen 18 und 80 Jahren
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess clinical efficacy of APN01 using a composite outcome of all cause-death or need of invasive mechanical ventilation up to 28 days
    E.2.2Secondary objectives of the trial
    To assess efficacy of APN01 using log transformed levels of Lactate dehydrogenase (LDH) as a surrogate marker for organ damage.
    To evaluate the safety of APN01 in patients with severe COVID-19
    To monitor other biomarker changes (e.g. IL-6, AngII) in patient with severe COVID-19 treated with APN01

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Hospitalised male or female, ≥ 18 to ≤ 80 years of age at the time of consent. The date of signing informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
    2. Diagnosed to be COVID-19 POSITIVE (SARS-CoV-2 nucleic acid – qPCR)
    3. Oxygenation criterion
    • Oxygen saturation ≤93 % (either on Room Air or while the patient is on supplement oxygen)
    4. ALT < 5xULN; bilirubin ≤ 1.5xULN
    5. Signed informed consent form
    E.4Principal exclusion criteria
    1. Any patient for whom the investigator does not consider there is a reasonable expecta-tion that they will be able to complete the study.
    2. Known history of positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody.
    3. Current or chronic history of liver disease (Child Pugh score ≥ 10), or known hepatic or biliary abnormalities (with the excep-tion of Gilbert's syndrome or asymptomatic gallstones).
    4. The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    5. Patients requiring high doses of loop diuretics (i.e. > 240 mg fu-rosemide daily) with significant intravascular volume depletion, as assessed clinically.
    6. History of sensitivity to any of the study medications, or compo-nents thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
    7. Pregnant females as determined by positive serum or urine hCG test prior to dosing.
    8. Lactating females.
    9. Unwillingness or inability to follow the procedures outlined in the protocol.
    10. Unstable Hemoglobin (Hb < 7) at time of drug infusion (i.e. Hb must be > 7 mg/dL at the time of drug infusion. Transfusion is permitted to increase Hb levels to allow entry into the study.
    11. Malignancy or other irreversible condition for which 6 month mortality is estimated to be >50%.
    12. Arterial blood pH less than 7.2 or serum HCO3- <15 (if ABG not available) before infusion is started.
    13. Known severe chronic pulmonary disease:
    - known FEV1/FVC less than 45% predicted, or
    - known chronic hypercapnia (PaCO2 > 45 mmHg) or chronic hypoxemia [(PaO2<55 mmHg) on FiO2 =0.21, or supplemental oxygen therapy prior to this admission], or
    - known FEV1 <15 ml/kg (e.g. 1L for 70 kg person), or
    - known radiographic evidence of chronic interstitial infil-tration, or
    - known hospitalization within the past six months for respiratory failure (PaCO2 > 50 mmHg or PaO2 < 55 mmHg, or oxygen saturation <88% on FiO2 = 0.21)
    - known chronic restrictive, obstructive, neuromuscular, chest wall, or pulmonary vascular disease resulting in severe exercise restriction (i.e. unable to climb stairs or perform household duties), known secondary polycythemia,
    severe pulmonary hypertension, or ventilator dependency
    14. Known vasculitis with diffuse alveolar hemorrhage
    15. Lung transplantation
    16. Pre-existing renal failure, i.e. requiring renal replacement ther-apy with hemodialysis or peritoneal dialysis
    17. There are other uncontrolled co-morbidities that increase the risks associated with the study drug administration, that are as-sessed by the medical expert team as unsuitable
    18. Patient in clinical trials with an IMP for COVID-19 within 30 days before signing informed consent form (ICF)
    19. Unstable hemodynamics in the preceding 4 hours (MAP ≤ 65 mmHg, or SAP < 90 mmHg, DAP < 60 mmHg, and vaso-active agents required)
    20. Immunocompromised patients (chemotherapy, HIV, organ transplants, stem cell transplants),
    21. Receive any Angiotensin-Converting-Enzyme inhibitor (ACEi) or renin inhibitor treatment within 7 days before ICF
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Continioulsy over the duration of the trial
    E.5.2Secondary end point(s)
    1. Log transformed levels of Lactate dehydrogenase (LDH) at day 5 as a surrogate marker for organ damage (powered secondary endpoint)
    2. 28-day mortality (all cause-death)
    3. Ventilator-free days (VFD) up to 28 days or hospital discharge
    4. Proportion of responders, defined as ≥2 improvement in WHO’s 11-Point Score system at day 7, 10, 14 and 28
    5. Time to death (all cause)
    6. Proportion of patients with any use of invasive mechanical ventilation up to 28 days or hospital discharge
    7. Time to first use of invasive mechanical ventilation up to 28 days or hospital discharge
    8. Absolute values and absolute change in P/F ratio over time
    9. Absolute values and absolute change in the modified Sequential organ failure assessment score (mSOFA score) over time
    10. Time to a 2-point decrease in WHO scoring scheme
    11. Absolute values and absolute change in lymphocyte counts over time
    12. Absolute values and absolute change in C-reactive protein levels over time
    13. Absolute values and absolute change in D-dimer over time
    14. Absolute values and absolute change in log transformed levels of LDH over time
    15. Time to hospital discharge
    16. Change in viral RNA over time
    Biomarker endpoints: Absolute values and absolute changes in relevant biomarkers over time:
    1. Angiotensin II (Ang II), Angiotensin 1-7 (Ang 1-7), Angiotensin 1-5 (Ang 1-5), renin and aldosterone, Angiotensin-converting enzyme (ACE), Angiotensin-converting enzyme 2 (ACE2), Angiotensin I (Ang I), Angiotensin 1-9 (Ang 1-9)
    2. Cytokines: Interleukin 6 (IL-6), Interleukin 8 (IL-8), soluble Tumor Necrosis Factor receptor type II (sTNFrII), Plasminogen Activator Inhibitor type-1 (PAI-1), von Willebrand Factor (vWF), Tumor necrosis factor-α (TNF-α)
    3. Alveolar epithelial markers: soluble Receptor for Advanced Glycation End products (sRAGE), Surfactant protein-D(SP-D)
    4. Endothelial markers: Angiopoietin-2
    5. Change in clinical laboratory markers associated with poor outcome over time (e.g., lymphocyte counts, hsTnI (high sensitivity troponin))
    6. NT-proBNP
    Safety endpoints:
    Frequency of adverse events (AEs) and serious adverse events (SAEs) in vital signs, clinical laboratory assessments and in ECG parameters
    E.5.2.1Timepoint(s) of evaluation of this end point
    Continioulsy over the duration of the trial
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Denmark
    Germany
    Russian Federation
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Overall End of Study is defined as the date of last patient last visit (LPO)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months8
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 120
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 200
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    SOC
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-04-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-10
    P. End of Trial
    P.End of Trial StatusOngoing
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